From the Guidelines
The relationship between microbiota and lean Non-Alcoholic Steatohepatitis (NASH) is characterized by distinct microbiota alterations, including increased intestinal permeability and altered bacterial species composition, which contribute to disease development and progression in non-obese individuals. According to the most recent study 1, lean NASH patients are associated with increased cardiovascular, liver, and all-cause mortality relative to those without NAFLD, highlighting the importance of understanding the microbiota-liver axis in this population.
The microbiota in lean NASH patients typically shows higher levels of certain bacterial species like Escherichia and Dorea, and decreased beneficial bacteria such as Faecalibacterium and Anaerosporobacter, as reported in a study published in Gastroenterology 1. These microbial imbalances promote inflammation through several mechanisms: increased translocation of bacterial products (particularly lipopolysaccharides) into the bloodstream, altered bile acid metabolism, production of harmful metabolites, and disruption of the intestinal barrier.
Some key points to consider in the relationship between microbiota and lean NASH include:
- Increased intestinal permeability and altered bacterial species composition contribute to disease development and progression
- Microbial imbalances promote inflammation through several mechanisms, including increased translocation of bacterial products and altered bile acid metabolism
- Genetic factors likely interact with these microbial changes in lean NASH patients
- Therapeutic approaches being investigated include probiotics, prebiotics, and fecal microbiota transplantation
- Dietary modifications emphasizing fiber-rich foods and limiting processed foods may help restore healthier microbial balance and potentially improve lean NASH outcomes.
In clinical practice, prioritizing the management of lean NASH should focus on addressing the underlying microbiota alterations and promoting a healthier microbial balance, as this may help improve disease outcomes and reduce the risk of complications, as suggested by the AGA Clinical Practice Update 1.
From the Research
Relationship Between Microbiota and Lean NASH
The relationship between microbiota and lean Non-Alcoholic Steatohepatitis (NASH) is complex and has been the subject of several studies.
- The gut microbiota affects hepatic carbohydrate and lipid metabolism as well as influences the balance between pro-inflammatory and anti-inflammatory effectors in the liver, thereby impacting NAFLD and its progression to NASH 2.
- Recent studies suggest that mitochondrial dysfunction promotes progression to NASH by aggravating the gut-liver status, and enhanced mitochondrial activity might reshape a specific microbiota signature that could delay NASH progression 3.
- The abundance of certain bacterial genera, such as Dorea and Oscillospira, may be increased in lean NASH patients, while others, such as AF12, Allboaculum, and Ruminococcus, may be reduced 3.
- The current studies suggest the role of gut microbiota in the development and progression of NASH, with mechanisms including modification of energy homeostasis, lipopolysaccharides (LPS)-endotoxemia, increased endogenous production of ethanol, and alteration in the metabolism of bile acid and choline 4.
Gut Microbiota Composition in Lean NASH Patients
- Lean NASH patients have a distinct gut microbiota composition compared to obese NASH patients and control groups, with differences in the abundance of certain bacterial genera such as Faecalibacterium, Ruminococcus, Lactobacillus, and Bifidobacterium 5.
- Liver fibrosis ≥ F2 was associated with increased abundance of Lactobacilli in NASH patients 5.
- Lean NASH patients had a 3-fold lower abundance of Faecalibacterium and Ruminococcus compared to obese NASH patients, and a deficiency in Lactobacillus compared to overweight and obese NASH patients 5.
Potential Therapeutic Approaches
- Modulation of the gut microbiota through diet control or the use of probiotics and prebiotics may offer new challenges for future studies 4, 6.
- Probiotics and prebiotics have shown promising results in animal studies and pilot clinical trials, with potential benefits including the enhancement of short-chain fatty acid production and the modulation of the gut-liver axis 6.